Tuberculosis (TB) remains a formidable global health challenge, and the rise of drug-resistant strains has made its treatment increasingly complex. In this study, we delve into the drug resistance patterns, mutation profiles, and clinical characteristics of Mycobacterium tuberculosis (MTB) isolates from Shaoxing, China, in 2024. But here's where it gets controversial: while DNA microarray assays offer rapid and interpretable results for detecting multidrug-resistant TB (MDR-TB), their limited mutation-detection scope and inability to identify resistance to second-line drugs raise questions about their standalone utility in clinical settings. And this is the part most people miss: the higher prevalence of drug resistance, including MDR-TB, in relapse cases compared to new cases highlights the critical need for individualized treatment strategies guided by both drug susceptibility testing and molecular profiling of resistance-associated mutations.
Tuberculosis, caused by the Mycobacterium tuberculosis complex, continues to be a leading cause of mortality from infectious diseases worldwide. According to the World Health Organization (WHO) Global TB Report 2024, an estimated 10.8 million new cases were reported in 2023, with approximately 400,000 being multidrug- or rifampicin-resistant (MDR/RR-TB). China, the third-largest contributor to the global TB burden, reported 741,000 new cases in 2023, with 29,000 being MDR/RR-TB. Drug-resistant TB (DR-TB) can arise from primary infection with resistant strains or develop during treatment due to factors like poor adherence, substandard drug quality, and inadequate infection control. The emergence of DR-TB, particularly MDR-TB, pre-extensively drug-resistant (pre-XDR), and extensively drug-resistant (XDR-TB) forms, significantly undermines treatment success and complicates clinical management.
In this context, our study aimed to characterize the drug resistance patterns and mutational profiles of MTB isolates from Shaoxing, Zhejiang, in 2024, and to examine the clinical features of affected patients. We collected samples from inpatients at the Affiliated Hospital of Shaoxing University, the designated center for TB and DR-TB treatment and research in Shaoxing. Patients were categorized into new cases and retreatment cases based on their treatment history. MTB culture, drug susceptibility testing, and DNA microarray detection were performed to assess resistance patterns and identify mutations associated with resistance to rifampicin (RIF) and isoniazid (INH).
Our findings revealed that 23.1% of the 268 MTB isolates exhibited resistance to at least one drug, with 6.0% being MDR. Among MDR-TB isolates, 1.1% were pre-XDR, and 0.4% were XDR. Mutational analysis using DNA microarray chips identified specific mutations in the rpoB and katG genes, as well as the inhA promoter, associated with RIF and INH resistance. Clinical analysis showed that relapse cases were more likely to occur in individuals over 50 years of age, be associated with pulmonary cavities, and exhibit higher rates of drug resistance, including MDR-TB, compared to new cases.
The use of DNA microarray assays provided rapid and interpretable results, making them a valuable tool for early identification of MDR-TB strains. However, their limitations, such as the inability to detect resistance to second-line drugs and uncommon mutations, underscore the need for their use in conjunction with conventional drug susceptibility testing. This study highlights the importance of individualized treatment strategies, guided by both drug susceptibility testing and molecular profiling, to effectively manage DR-TB and reduce its global burden.
Thought-provoking question: Given the limitations of DNA microarray assays, should they be considered a primary diagnostic tool for MDR-TB, or should their use be restricted to adjunctive roles alongside conventional methods? We invite readers to share their perspectives in the comments, fostering a discussion on the optimal integration of these technologies in TB management.
